2. Forward-Looking Statements
2
Except for statements of historical fact, the statements in this presentation are forward-looking statements, including statements
regarding the future development of our proprietary Engineered Toxin Body (ETB) technology; the future development of
evofosfamide; our milestones; our plans to enter the clinic with multiple candidates; our expected receipt of clinical data; and our
future cash needs. These statements constitute "forward-looking statements" within the meaning of Section 27A of the Securities
Act and Section 21E of the Securities Exchange Act and are usually identified by the use of words such as "anticipates,"
"believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or
similar expressions. These forward-looking statements reflect our current views about our plans, intentions, expectations,
strategies and prospects, which are based on the information currently available to us and on assumptions we have made.
Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those
forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be
attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and
will be affected by a variety of risks and factors that are beyond our control. These statements involve risks and uncertainties that
can cause actual results to differ materially from those in such forward-looking statements. Important factors that may cause
actual results to differ materially from the results discussed in the forward-looking statements include risks and uncertainties,
including our failure to secure and maintain relationships with collaborators; (2) risks relating to clinical trials and other
uncertainties of product candidate development; (3) risks relating to the commercialization, if any, of our proposed product
candidates (such as marketing, regulatory, product liability, supply, competition, and other risks); (4) dependence on the efforts of
third parties including our strategic partners; and (5) dependence on intellectual property. Further information regarding these and
other risks is included under the heading "Risk Factors" in our filings with the Securities and Exchange Commission available from
the SEC's website (www.sec.gov). Existing and prospective investors are cautioned not to place undue reliance on these forward-
looking statements, which speak only as of the date hereof.
3. Molecular Templates (NASDAQ: MTEM)
MTEM is a clinical stage oncology company with a differentiated platform
o Lead compound has a novel mechanism of action, good safety, and Phase I monotherapy activity in heavily pre-treated
DLBCL patients
o 2nd-generation compounds have increased potency and reduced innate and adaptive immunogenicity in animal models
o 3rd-generation compounds add novel immuno-oncology approach to 2nd-generation constructs
o Recent $20M Takeda Pharma investment and multi-target research collaboration validate technological approach
MTEM completed a reverse merger with public company Threshold Pharmaceuticals on 8/1/2017
o A $40M private placement led by Longitude Ventures, CAM Capital, BVF, Perceptive Advisors and others closed
simultaneously with the reverse merger
o Upon closing of the reverse merger, we had more than $75M in cash and cash equivalents with more than 2+ years of
runway based on current plans
MTEM has multiple milestones over the next 24 months
o Clinical data on lead compound MT-3724
o Multiple new agents to enter clinic in 2018
o Continued development of evofosfamide
3
5. Shiga-Like Toxin A (SLT-A) has well defined biological properties
Unique SLT-A Biological Properties
o Can force receptor internalization
o Self-routes to the cytosol
o Irreversibly and enzymatically inactivates ribosomes activity to destroy target cells
• Novel intracellular mechanism of cell-kill aimed at major tumor requirement (protein synthesis)
• Exceptionally potent
SLT produced by certain E. coli strains
o SLT is 99% identical to Shiga toxin
SLT comprised of A and B subunits
B-subunit binds CD77 receptor
o CD77 is a glycosphingolipid that does
not normally internalize
A-subunit (SLT-A) internalizes, self-routes
to cytosol, and inactivates ribosome Shiga-Like Toxin
(SLT)
5
A
B
6. SLT-A based engineered immunotoxins are potent
SLT-A Subunit
o Forces cell entry
o Self-routes inside in the cell
o Enzymatic and irreversible
ribosome de-purination
SLT-B Subunit
o Binds CD77 (Gb3) – a non-
internalizing glycosphingolipid
Modified SLT-A
o Engineered from SLT-A
o Retains biological properties of
SLT-A parent
o De-Immunized using in-house
proprietary methods
Engineered Toxin Bodies: Biological Properties
A
VL VH
HIGH POTENCY
A
VL VH
REDUCED
IMMUNOGENICITY
Single-Chain Variable
Fragment
SLT-A Derived ✓ Forced Receptor Internalization ✓ Novel MOA – Ribosome Inactivation ✓ Intracellular Routing
MTEM Engineered ✓ High-Affinity & Specific Binding ✓ De-Immunized SLT-A Scaffold ✓ Antigen Seeding
Immunological ✓ Delivery of foreign antigens to tumor microenvironment ✓ Cross-priming
6
A
B
7. MTEM’s proprietary ETB platform is differentiated
ANTIBODY ADC CAR-T CD3 BISPECIFIC ETB
Mechanism
of Action (MOA)
ADCC/CDC Chemotherapy T-cell engagement T-cell engagement
Novel MOA
(ribosomal destruction)
Target
Does not need to
internalize
Must internalize
Does not need to
internalize
Does not need to
internalize
Does not need to
internalize
Resistance
Mechanism
Change to tumor
microenvironment
Chemo-resistance
Change to tumor
microenvironment
Change to tumor
microenvironment
Unknown
Manufacturing Off-the-shelf Off-the-shelf Autologous Off-the-shelf Off-the-shelf
Solid Tumor Yes Yes No No Yes
7
VL VH
VL VH
VL VH
Signaling
Domains
9. MT-3724, a 1st generation ETB, is a novel approach to target CD20
Rituximab
o Binds CD20 (does not internalize)
o Destroys tumor cells by ADCC/CDC
Bexxar & Zevalin
o Bind CD20 (do not internalize)
o Destroy tumor cells by localized radiation
MT-3724
o 1st generation ETB
o Binds CD20 and forces internalization
o Competes with Rituxan for CD20 binding
o Cell-kill by enzymatic ribosome destruction
9
• ~20,000 patients/yr with
NHL die in US each year
• These patients fail current
CD20 therapies
• However, >90% of patients
retain CD20 expression
after failure
• CD20 does not internalize
so ADCs not feasible
10. Rituximab and MT-3724 have similar Kds and compete for CD20 binding
10
Rituximab blocks
MT-3724 activity
Similar binding affinity for
CD20+ cells as rituximab
o CD20 has a small extracellular domain
o Approved CD20 antibodies compete for binding to CD20
11. Overview of MT-3724 phase I trial in NHL patients
Baseline Characteristics1
Monotherapy 3+3 Dose-Escalation Study in NHL
o Failed chemo and CD20 antibody therapy, all subtypes
o 1st cycle: 2 weeks on (M-W-F), 2 weeks off of dosing
o Subsequent cycles are 2 weeks on (M-W-F), 1 week off
o MTD is assessed from cycle 1
o Efficacy scans are conducted after cycle 2 and 4
o Patients could originally only receive up to 5 cycles of
drug: new amendment to allow continued dosing
o Conducted at 3 sites (MSK, MDACC, UNC)
Characteristics All Doses (N = 21)
Median Age, years (range) 67 (34-78)
Prior Therapies, median (range) 4 (1-11)
< 4, n (%) 5 (24%)
≥ 4, n (%) 16 (76%)
NHL Subtype, n (%)
DLBCL 152 (71%)
FL 4 (19%)
MCL 2 (10%)
1) Subtype data has been adjusted post Dec 2016 ASH presentation
2) Two patients were of mixed histology
11
14. 7/30/15
(Cycle 5)
4/14/15
(Cycle 2)
5/28/15
(Cycle 4)
2/27/15
(Baseline)
o 77 y/o R-CHOP refractory tx DLBCL patient
TUMOR RESPONSE IN FULLY
RESISTANT DIFFUSE LARGE
B-CELL LYMPHOMA (DLBCL)
PATIENT
14
PET Image of Patient 2001 (5 mcg/kg)
15. DLBCL Pts with Rituxan <1,000 ng/mL History Age Outcome
2001: txDLBCL (5 mcg/kg)
MT-3724 LEVELS: 24 ng/mL
• Relapsed R-Bendamustine
• Refractory to 5 cycles of R-CHOP
77 PR
1001: Primary DLBCL (10 mcg/kg)
MT-3724 LEVELS: 135 ng/mL
• R-CHOP
73 SD (19% ↓ in tumor volume; left after C2)
1004: Primary DLBCL (20 mcg/kg)
MT-3724 LEVELS: 87 ng/mL
• 6 cycles of R-CHOP: remission within 6 months
• 3 cycles of RICE: Progressive disease
• 2 cycles of R-DAHP: PR w/ Autologus SCT
• Relapse from autologous SCT
50 CRuAlloSCT
4001: Primary DLBCL (50 mcg/kg)
MT-3724 LEVELS: 326 ng/mL
• R-V-EPOCH
• R-CHOP
72 PD
1007: Primary DLBCL (75 mcg/kg)
MT-3724 LEVELS: 204 ng/mL
• R-CHOP + Etoposide: Progression within 6 mths
• R-EPOCHX4, R-CHOPx2: Progression within 6 mths
• Methotrexate+R-GDP: Progression within 6 mths
• Whole brain radiation: Progression within 6 mths
• PNT2258: Progression within 6 mths
62 Withdrew/PD
4003: Primary DLBCL (75 mcg/kg)
MT-3724 LEVELS: 668 ng/mL
• R-CHOP with CR of 3+ yr duration
• RICE with CR
• ASCT (relapse <14 mths)
62 SD (48%↓ in tumor volume)
4002: Primary DLBCL (100 mcg/kg)
MT-3724 LEVELS: 579 ng/mL
• R-CHOP; R-CVP; R-bendamustine; R-ICE
• R-GEM/OX
• ASCT
60 DLT (49%↓ in tumor volume, 2 doses)
1006: Primary MCL w/ txDLBCL (100 mcg/kg)
MT-3724 LEVELS: 1030 ng/mL
• R-CHOP and R-CVS
• RICE
• TKI
• Revlimid
• CD30-ADC
69 DLT
15
Activity in DLBCL patients with low levels (<1,000 ng/mL) of Rituxan
16. MT-3724 demonstrated promising results in a Phase I in DLBCL
Efficacy
• Robust B-cell depletion; no meaningful anti-drug antibodies
• Multiple patients with significant clinical benefit
• Responses seen in patients who had failed multiple prior regimens
Safety/tolerability
• Very well tolerated
• Infusions ~2 hours with only prednisone co-administration
• No infusion reactions
DLT
• Non-life-threatening
• Symptoms resolved upon cessation of dosing
• Likely mediated by innate immune systems (reported with other bacterial proteins)
Phase II program to initiate by end of year
• Expansion of monotherapy data in rel/ref DLBCL
• Combination with chemotherapy in earlier lines of treatment in DLBCL
16
18. 2nd generation ETB scaffold overview
1st generation
• High Potency
A
VL VH
HIGH POTENCY
A
VL VH
REDUCED
IMMUNOGENICITY
ANTIGEN SEEDIN
A
VL VH
• Improved engineering of molecule (fit between SLTA and scFv)
• Engineered scaffold for reduced innate (safety) and adaptive (potency) immunity
Higher Potency and De-Immunized
18
2nd generation
• Higher Potency
• De-immunized
19. MT-4019: 2nd generation ETB targeting CD38 entering clinic in 2018
19
MT-4019
CD38 is an ectoenzyme central to disease
o Daratumumab has unprecedented single agent activity
Daratumumab failures retain CD38 expression
o Patients who progress on Daratumumab therapy show increase in
CD55/CD59 levels
o CD55 and CD59 are complement inhibiting proteins
CD38 is poorly-internalizing
o ADCs are not a viable strategy to target CD38
MT-4019 overview
o 2nd generation ETB
o pM activity against CD38+ cells (10-100-fold more potent than MT-3724)
o Activity in low CD38, high CD55/CD59-expressing (Darzalex-resistant) cells
o Dramatically reduced ADA and innate response in murine and NHP model
o Synergistic activity with IMiDs and proteasome inhibitors
20. Cell Line Type CD38 Expression
(MFI)
CD55/CD59
Expression
CD50
H929 Multiple myeloma 55,000 >50,000 16pM
Daudi B-lymphoblast 166,000 <20,000 58pM
ST486 B-lymphoblast 129,000 <20,000 41pM
MOLP-8 Multiple myeloma 146,000 >50,000 228pM
BC3 B-lymphocyte 79,000 <20,000 180pM
IM-9 Multiple myeloma - ND >>100nM
HDLM-2 B-lymphoblast - ND >>100nM
L1236 B-lymphoblast - ND >>100nM
Summary of Cell-Kill Activity for MT-4019ND
MT-4019ND has potent activity against low CD38, high CD55/CD59 expression
o MT-4019ND activity not dependent on tumor microenvironment
o Enzymatic activity does not require high CD38 levels
20
No Correlation Between CD38 Level and IC50
MT-4019: Potent activity with differentiated mechanism versus daratumumab
21. 21
• Shiga toxin scaffold is known to bind innate TLR-4 receptors on neutrophils and monocytes
• Innate immune recognition drives capillary leak syndrome in patients
• Alterations made in 2nd-generation scaffold inhibit neutrophil and monocyte activation in
non-human primate studies
MT-4019: 2nd-generation scaffold has reduced innate immune recognition
22. 22
• NHPs treated at 50 mcg/kg with MT-3724 showed hunched posture and decreased activity
• No NHPs treated at 50 mcg/kg with MT-4019 showed hunched posture or decreased activity
• No monocyte or neutrophil activiation seen with MT-4019
MT-4019: 2nd-generation scaffold shows reduced innate toxicity in NHPs
Comparison of Key Toxicities Between MT-3724 and MT-4019
MT-3724, 0.05 mg/kg/dose: n= 6 (3M, 3F)
Study 2205-003 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Dosed X X X X X X
activity decreased 100% 50% 50% 100% 50%
hunched posture 83% 100%
inappetance 100% 50% 83% 50% 50%
MT-4019, 0.05 mg/kg/dose: n=2 (2F)
Study 2205-008 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Dosed X X X X X X
activity decreased
hunched posture
inappetance 100% 50% 100%
23. 23
• ADA response in repeat-dose murine and cynomolgus models is dramatically diminished
• Reduction in adaptive immune recognition allows for solid tumor dosing using 2nd-
generation scaffold
MT-4019: 2nd-generation scaffold has reduced adaptive immune recognition
CD38 scFv-SLTA: 0.05 mg/Kg
CD38 scFv-de-immunized SLTA: 0.05 mg/Kg
ADA Response in NHPs Across Two Dosing Cycles
Reduced Immunogenicity of
MT-4019ND in Mice
24. 2nd generation ETBs targeting solid tumors to enter clinic in 2018
24
HER2
o HER2 receptor persists after failure of other
modalities (antibody, TKI, ADC)
o Lead ETB compound is non-competitive with
trastuzumab / trastuzumab-DM1
o Novel mechanism of action
• Up to 50-fold more potent than Kadcyla®
• Active in Kadcyla ® -resistant cells
• Additive or synergistic activity with Kadcyla ®
o Improved tumor penetration
o Lead compound to enter clinic in 2018
Lead Criteria
PD-L1
Lead Criteria
o PD-L1 is central target on tumors that persists
after antibody failure
• ~1/3 of patients respond to checkpoint
inhibitors despite target presence
o Lead ETB compound can force internalization
• PD-L1 does not efficiently internalize
• Not appropriate target for ADCs
o Novel MOA not dependent on presence of
infiltrating T-cells for cell-kill
o Improved tumor penetration
• 1/3 size of traditional antibody
o Lead compound to enter clinic in 2018
26. 3rd generation ETB scaffold adds immuno-oncology activity to platform
A
VL VH
HIGH POTENCY
A
VL VH
REDUCED
IMMUNOGENICITY
ANTIGEN SEEDING
A
VL VH
“Antigen Seeding” capability
represents the next generation
immuno-oncology approach
Higher Potency and De-Immunized
Next-Gen
Immune Oncology
26
• Improved engineering of molecule (fit between SLTA and scFv)
• Engineered scaffold for reduced innate (safety) and adaptive
(potency) immunity
1st generation
• High Potency
2nd generation
• Higher Potency
• De-immunized
3rd generation
• Higher Potency
• De-immunized
• Antigen seeding
27. SLT-A scaffold can deliver
payload of MHC-I antigens
for cell surface presentation
3rd generation ETB scaffold incorporates immuno-oncology activity
Nucleus
Golgi
Endoplasmic
Reticulum
Endosome
Cytosol
A
VL VH
A
VLVH
A
VL
VH
A
VL
VH
A
VL
VH
A
VL VH
A
VL
VH
Cleaved
Antigen
ETB with Class I
Viral Antigen Target
Cytotoxic
T-Cells
TCR
MHC-I
Antigen/MHC-I
Complex
A
VL
VH
o Fusion of Class I viral dominant
antigen to Engineered Toxin Body
o Create high frequency & high avidity
effector T-cell response to tumor
o Dual mechanism of cell-kill
✓ Potential to recruit high-avidity T-
cell response to tumor without
sacrificing SLTA-mediated cell-kill
Antigen Seeding Technology (AST)
27
28. CMV-specific CD8+ T-cells undergo unique progressive expansion (memory inflation) and accumulate in periphery
o Up to 20% of T-cells in elderly hosts are specific to pp65
CMV-specific CD8+ T-cells may be resistant to exhaustion (decreased PD-1, CD160, CD244 expression)
o CMV-specific CD8+ T-cells in CLL patients are not exhausted whereas non-CMV specific T-cells are exhausted
Lead 3rd gen. ETB adds antigen seeding to PD-L1 targeting construct
Detection of CMV MHC Class I Complex on Intoxicated Cells
L1236(PD-L1+)cellcount
CMV-pp65 TCR multimer- PE
- PBS treated cells
- PD-L1 ETB no antigen
- PD-L1 ETB/ CMV
antigen
TCR Specific Detection of Surface MHC I/
CMV antigen complex
28
• MDA-MB231 treated with ETB for 4 hrs and washed
• Control- or CMV-reactive T-cells added
• CMV-dependent cell-kill observed
MDA-MB231 + Cntrl T cells MDA-MB231 + CMV T cells
20000
40000
60000
80000
0
30000
40000
50000
60000
20000
30. MTEM is a clinical stage oncology company with a distinctive platform
Lead compound (MT-3724) has novel mechanism of action, good safety, and monotherapy activity
o Proof-of-concept for internalization of non-internalizing receptors (CD20)
o Novel mechanism of cell-kill is active in a Phase I of DLBCL patients refractory to chemotherapy
o Safety profile is differentiated and we believe may be combinable with chemotherapy
2nd generation ETBs are more potent with reduced immunogenicity
o MT-4019 targets CD38, a validated target, with extremely high potency and will enter the clinic in 2018
o De-immunized constructs targeting solid tumors (Her2 and PD-L1) will also enter the clinic in 2018
3rd generation ETBs add novel immuno-oncology dimension to 2nd generation constructs
Forced internalization and novel cell-kill mechanism provides alternative biology to ADC platforms
o Clinical data highlight benefits of ETB approach
o Multiple clinical milestones around lead program and next-generation ETBs over next 18 months
30